Synthesis of a radiolabeled enniatin cyclodepsipeptide [3H-methyl]JES 1798

✍ Scribed by U. Pleiss; A. Turberg; A. Harder; M. Londershausen; P. Jeschke; G. Boheim

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 396 KB
• Volume: 38
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199607)38:7<651::aid-jlcr881>3.0.co;2-s

✦ Synopsis

For receptor binding studies and the elucidation of the mode of action of the potent anthelmintic compound JES 1798 a tritium labeled compound at very high specific activity was necessary. Tritium was introduced by methylation of the N-demethyl precursor JES 2314. The identity of m-methyl-3H]JkS 1798 was determined by mass spectrometry.

After synthesis and purification, 535 pg [N-methyl-3H]JES 1798 were available at a specific activity of 84 Ci/mmol (3.1 1 TBqhmol) as determined by mass spectrometry.

The total activity was 80 mCi (2.96 GBq).

Radiolabeled JES 1798 showed an efficient and specific binding to a membrane fraction from Ascaris suum. Displacement by unlabeled JES 1798 was half-maximal at about 0.72 k 0.06 pM. Different known enniatins also competed for the [3H]JES 1798-binding in the Ascaris suum membrane preparation. In vitro comparison of JES 1798 with enniatin A, A,, B and B, or beauvericin revealed that enniatin A showed an anthelmintic activity against Nippostrongylus brasiliensis, Tichinella spiralis and Heterakis spumosa at a concentration of 5 pdml, whereas enniatins A,, B and B, had an activity at concentrations between 1 and 100 pg/ml. On the other hand beauvericin and JES 1798 exerted their anthelmintic activities at 100 pdml and therefore possess minor anthelmintic potency in vitro as compared to the natural occurring enniatins